Glycopeptides

*History of Glycopeptides:*

1. *Discovery:*

   - Vancomycin was discovered in 1953 from soil bacteria (*Amycolatopsis orientalis*).

   - It was developed as an alternative to penicillin for resistant bacteria.

2. *Early Use:*

   - Used in the 1950s and 1960s as a last-resort treatment for resistant bacteria, but it had side effects like kidney and ear damage.

3. *New Development:*

   - In the 1980s, *Teicoplanin* was developed as an alternative to vancomycin with fewer side effects and a longer half-life.

4. *Resistance:*

   - In the 1990s, resistant strains like *VRE* (Vancomycin-Resistant Enterococci) emerged.

5. *Modern Drugs:*

   - New drugs like *Dalbavancin* and *Oritavancin* were developed to combat resistance.

6. *Current Importance:*

   - Glycopeptides remain essential for treating serious infections like *MRSA*, but they must be used cautiously to avoid resistance

- Glycopeptides work by *inhibiting bacterial cell wall synthesis*.  

- They bind to the *D-Ala-D-Ala terminus* of peptidoglycan precursors, which are essential components for building the bacterial cell wall.   

-This binding prevents the incorporation of new peptidoglycan units into the growing cell wall.  

- As a result, the bacterial cell wall becomes weak and unstable, leading to *cell lysis and death*.

- Glycopeptides are used to treat serious infections such as:

  - Bloodstream infections.

  - Skin and soft tissue infections.

  - Bone and joint infections.

  - Lower respiratory tract infections.

  - Multi-resistant infections, such as those caused by Gram-positive bacteria.

- Nausea and vomiting  

- Skin rash  

- Kidney problems (nephrotoxicity)  

- Ear toxicity (ototoxicity), especially with high doses of Vancomycin

1. Symptoms:*

- Symptoms associated with the use of glycopeptides include:

  - *Gastrointestinal symptoms:*

    - Nausea.

    - Vomiting.

    - Diarrhea.

  - *Allergic reactions:*

    - Skin rash.

    - Itching.

    - Swelling of the face or throat (rare).

  - *Toxicity-related symptoms:*

    - Hearing loss or ringing in the ears (Ototoxicity).

    - Kidney dysfunction (Nephrotoxicity).

  - *Rare symptoms:*

    - Fever.

    - Low blood pressure (in case of rapid infusion of Vancomycin).

### *2. Management:*

- Managing treatment with glycopeptides requires careful monitoring to avoid side effects and ensure drug efficacy. Key management steps include:

#### *A. Dosage Monitoring:*

- The dose should be carefully determined based on the patient’s weight and kidney function.

- Measure drug levels in the blood (e.g., *Trough Levels*) to ensure the dose is effective and not toxic.

#### *B. Monitoring Vital Functions:*

- *Kidney function:* Regular tests for kidney function (e.g., creatinine levels).

- *Ear function:* Monitor for signs of hearing loss or tinnitus.

#### *C. Handling Side Effects:*

- If symptoms like skin rash or kidney problems appear, adjust the dose or temporarily stop the medication.

- Severe diarrhea may indicate *Clostridioides difficile colitis*, a complication of antibiotic use.

#### *D. Education and Guidelines:*

- Educate patients on the importance of completing the prescribed dose and not stopping the medication without consulting a doctor.

- If administered intravenously, infuse slowly to avoid "Red Man Syndrome," an allergic reaction caused by rapid infusion.

- Caution should be exercised when using these drugs in patients with kidney failure.

- They are not recommended during pregnancy or breastfeeding unless the benefits outweigh the risks.

- Drug levels in the blood should be monitored to avoid overdosing.

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